Show simple item record

dc.contributor.advisorJennifer Wangen_US
dc.contributor.authorKyawe, Pyae Phyo
dc.date.accessioned2024-01-30T15:06:23Z
dc.date.available2024-01-30T15:06:23Z
dc.date.issued2023-12-18
dc.identifier.doi10.13028/zybt-n415
dc.identifier.urihttp://hdl.handle.net/20.500.14038/53008
dc.description.abstractInfluenza A virus (IAV) is a respiratory pathogen with a segmented negative-sense RNA genome that is capable of causing epidemics and pandemics. During the 2021-2022 influenza season, approximately 9 million people in the U.S. were infected with influenza, resulting in an estimated 5,000 deaths. The error-prone nature of the IAV polymerase results in antigenic drift and antigenic shift which contribute to low vaccine efficacy and escape from antivirals. Furthermore, the host factors required for the complete IAV infectious cycle have not been fully identified. The aim of this dissertation is to examine the host factors that may contribute to IAV infectivity in human lung cells. My goal is to understand how changes in the expression levels of host factors can impact influenza infection by CRISPR-mediated knockout or overexpression of target genes. Utilizing CRISPR screens, several candidates, whose up- or down-regulation resulted in reduced IAV infection in the human A549 cell line were identified. I confirmed that the knockout of CMAS or overexpression of B4GALNT2 inhibited IAV infection. In addition, I tested whether overexpression of two candidates from the CRISPR activation screen – DEFB127 and ADAR1 – would inhibit IAV and non-IAV viruses. Surprisingly, overexpression of the two candidates had minimal impact on IAV in A549 cells, but overexpression of ADAR1 had a pro-viral effect on other viruses. Taken together, these data provide insight into host factors modulating IAV infection and how CRISPR-mediated gene modulation can be utilized to further understand the IAV life cycle and for development of therapeutic agents for flu.en_US
dc.language.isoen_USen_US
dc.publisherUMass Chan Medical Schoolen_US
dc.rightsCopyright © 2023 Pyae Phyo Kyaween_US
dc.rights.uriAll Rights Reserveden_US
dc.subjectinfluenzaen_US
dc.subjectvirusen_US
dc.subjectCRISPR-Cas9en_US
dc.titleAn exploration of influenza A virus entry factors using CRISPR-based gene editingen_US
dc.typeDoctoral Dissertationen_US
atmire.contributor.authoremailPyae.Kyawe@umassmed.eduen_US
dc.contributor.departmentDiabetes Center of Excellenceen_US
dc.description.thesisprogramInterdisciplinaryen_US
dc.identifier.orcid0000-0002-8259-6017en_US


Files in this item

Thumbnail
Name:
PPK THESIS 2024-01-22.pdf
Embargo:
2025-12-18
Size:
2.280Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record